What's the difference between Hb S & Hb C althought the two are caused due to substitution of glutamate residues at the B-globin chain?

The difference here is in the folding pattern of B-globin chains; In Hb S, the glutamate residue (polar negatively charged) is being substituted by a valine residue which is non polar neutral branched chain AA. This will affect the folding of the B-globin by a certain way causing sickliness of the cells in hypoxic conditions. This sickliness is due to that the valine residues tend to create hydrophobic patches on the B-globin to stick together.

Hypoxia aggravates this condition. In Hb C, same glutamate residue is being substituted by a lysine residue which is polar positively charged AA. This will affect folding of B-globin chain in another way that is different from Hb S.

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